chr5-178247795-G-T

Position:

• chr5-178247795-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_173465.4(COL23A1):​c.1249C>A​(p.Pro417Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: COL23A1 NM_173465.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.91

Genes affected

COL23A1 (HGNC:22990): (collagen type XXIII alpha 1 chain) COL23A1 is a member of the transmembrane collagens, a subfamily of the nonfibrillar collagens that contain a single pass hydrophobic transmembrane domain (Banyard et al., 2003 [PubMed 12644459]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL23A1	NM_173465.4	c.1249C>A	p.Pro417Thr	missense_variant	21/29	ENST00000390654.8	NP_775736.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL23A1	ENST00000390654.8	c.1249C>A	p.Pro417Thr	missense_variant	21/29	5	NM_173465.4	ENSP00000375069.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 08, 2024

The c.1249C>A (p.P417T) alteration is located in exon 21 (coding exon 21) of the COL23A1 gene. This alteration results from a C to A substitution at nucleotide position 1249, causing the proline (P) at amino acid position 417 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.030
CADD	Uncertain	24
DANN	Benign	0.94
DEOGEN2	Benign	0.24	T;.
Eigen	Benign	0.031
Eigen_PC	Benign	-0.083
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.65	T;T
M_CAP	Pathogenic	0.39	D
MetaRNN	Uncertain	0.66	D;D
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Benign	1.9	L;.
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.6	N;.
REVEL	Uncertain	0.53
Sift	Benign	0.15	T;.
Sift4G	Benign	0.11	T;T
Polyphen		0.99	D;.
Vest4		0.56
MutPred		0.41		Gain of phosphorylation at P417 (P = 0.0023);.;
MVP		0.91
MPC		0.60
ClinPred		0.81	D
GERP RS		3.7
Varity_R		0.10
gMVP		0.36

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-177674796;